chr2-161796852-T-A

Variant names:

• chr2-161796852-T-A
• rs1551051
• NM_001178015.2:c.131-7597T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001178015.2(SLC4A10):​c.131-7597T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,088 control chromosomes in the GnomAD database, including 48,553 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48553 hom., cov: 32)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 1 publications found

Genes affected

SLC4A10 (HGNC:13811): (solute carrier family 4 member 10) This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

SLC4A10 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia and characteristic brain abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Baylor College of Medicine Research Center, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A10	NM_001178015.2	c.131-7597T>A		intron_variant	Intron 2 of 26	ENST00000446997.6	NP_001171486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A10	ENST00000446997.6	c.131-7597T>A		intron_variant	Intron 2 of 26	1	NM_001178015.2	ENSP00000393066.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120394 AN: 151970 Hom.: 48494 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.762

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.792 AC: 120501 AN: 152088 Hom.: 48553 Cov.: 32 AF XY: 0.791 AC XY: 58793 AN XY: 74358

African (AFR) AF: 0.933 AC: 38727 AN: 41520

American (AMR) AF: 0.660 AC: 10069 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2442 AN: 3472

East Asian (EAS) AF: 0.982 AC: 5071 AN: 5164

South Asian (SAS) AF: 0.721 AC: 3477 AN: 4824

European-Finnish (FIN) AF: 0.764 AC: 8072 AN: 10566

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50174 AN: 67972

Other (OTH) AF: 0.765 AC: 1612 AN: 2106

Alfa AF: 0.775 Hom.: 5746

Bravo AF: 0.790

Asia WGS AF: 0.852 AC: 2952 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.84
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1551051; hg19: chr2-162653362;